Gene Patents Overturned — and Scalia’s Weird Dissenting Opinion

So, the Supreme Court just ruled that Myriad Genetics does not, in fact, have the right to patent two naturally occurring human genes, BRCA1 and BRCA2. This is good news, because . . . well, because patenting a gene is total bullshit.

If you’re not familiar, these two genes are important because genetic variation in their DNA sequences has been linked to breast cancer. So, the sequence of your DNA in these two genes can reveal if you have a higher-than-average risk of developing breast cancer. It was exactly this sort of test that prompted Angelina Jolie to undergo a preemptive double mastectomy.

The problem is that the tests were really, really expensive, because of Myriad’s patents. So, the immediate consequence of the ruling should be that the prices for these tests should come way, way down.

The opinion (PDF here, if you’re interested) focuses on the difference between “discovering” something — like the sequence or location of a gene — and “creating” something — like a thing that can be patented. So, a gene is a naturally occurring thing that can not be patented. However, if you take the mRNA from a gene and reverse-transcribe it to make cDNA, this new thing might still be patentable. But, the ruling explicitly notes that the cDNA would be a creation because of the removal of introns. So, cDNA from a single-exon gene might not be patentable.

The ruling explicitly states that it offers no opinion on the patentability of genes that have had their DNA sequences deliberately altered — leaving that question for another day.

It also points out limitations of the ruling with respect to plants. The goal here seems to be to ensure that this ruling is not interpreted as invalidating any plant patents covering plant strains that have been developed through selective breeding.

That all seems pretty straightforward. The ruling does seem to leave a number of issues surrounding the patenting of genetic material unresolved, but it is quite clear about which issues it is kicking down the field.

But then there’s this bit of weirdness at the end.

The opinion is pretty much unanimous, which is always nice. Except for a little, tiny bit of dissension from Antonin Scalia. Here is the complete text of his dissenting opinion:

I join the judgment of the Court, and all of its opinion except Part I–A and some portions of the rest of the opinion going into fine details of molecular biology. I am unable to affirm those details on my own knowledge or even my own belief. It suffices for me to affirm, having studied the opinions below and the expert briefs presented here, that the portion of DNA isolated from its natural state sought to be patented is identical to that portion of the DNA in its natural state; and that complementary DNA (cDNA) is a synthetic creation not normally present in nature.

I actually thought Part 1-A of the ruling was a little weird when I first read it. Not because it said anything strange or controversial, but because it read sort of like a Wikipedia entry on basic genetics, and contains a lot of details that don’t seem particularly relevant?.

Here’s the full text of the part of the ruling about which Scalia says, “I am unable to affirm those details on my own knowledge or even my own belief.”

Genes form the basis for hereditary traits in living organisms. See generally Association for Molecular Pathology v. United States Patent andTrademark Office, 702 F. Supp. 2d 181, 192–211 (SDNY 2010). The human genome consists of approximately 22,000 genes packed into 23 pairs of chromosomes. Each gene is encoded as DNA, which takes the shape of the familiar “double helix” that Doctors James Watson and Francis Crick first described in 1953. Each “cross-bar” in the DNA helix consists of two chemically joined nucleotides. The possible nucleotides are adenine (A), thymine (T), cytosine (C), and guanine (G), each of which binds naturally with another nucleotide: A pairs with T; C pairs with G. The nucleotide cross-bars are chemically connected to a sugar-phosphate backbone that forms the outside framework of the DNA helix. Sequences of DNA nucleotides contain the information necessary to create strings of amino acids, which in turn are used in the body to build proteins. Only some DNA nucleotides, however, code for amino acids; these nucleotides are known as “exons.” Nucleotides that do not code for amino acids, in contrast, are known as “introns.”

Creation of proteins from DNA involves two principal steps, known as transcription and translation. In transcription, the bonds between DNA nucleotides separate, and the DNA helix unwinds into two single strands. A single strand is used as a template to create a complementary ribonucleic acid (RNA) strand. The nucleotides on the DNA strand pair naturally with their counterparts, with the exception that RNA uses the nucleotide base uracil (U) instead of thymine (T). Transcription results in a single strand RNA molecule, known as pre-RNA, whose nucleotides form an inverse image of the DNA strand from which it was created. Pre-RNA still contains nucleotides corresponding to both the exons and introns in the DNA molecule. The pre-RNA is then naturally “spliced” by the physical removal of the introns. The resulting product is a strand of RNA that contains nucleotides corresponding only to the exons from the original DNA strand. The exons-only strand is known as messenger RNA (mRNA), which creates amino acids through translation. In translation, cellular structures known as ribosomes read each set of three nucleotides, known as codons, in the mRNA. Each codon either tells the ribosomes which of the 20 possible amino acids to synthesize or provides a stop signal that ends amino acid production.

DNA’s informational sequences and the processes that create mRNA, amino acids, and proteins occur naturally within cells. Scientists can, however, extract DNA from cells using well known laboratory methods. These methods allow scientists to isolate specific segments of DNA — for instance, a particular gene or part of a gene—which can then be further studied, manipulated, or used. It is also possible to create DNA synthetically through processes similarly well known in the field of genetics. One such method begins with an mRNA molecule and uses the natural bonding properties of nucleotides to create a new, synthetic DNA molecule. The result is the inverse of the mRNA’s inverse image of the original DNA, with one important distinction: Because the natural creation of mRNA involves splicing that removes introns, the synthetic DNA created from mRNA also contains only the exon sequences. This synthetic DNA created in the laboratory from mRNA is known as complementary DNA (cDNA).

Changes in the genetic sequence are called mutations. Mutations can be as small as the alteration of a single nucleotide—a change affecting only one letter in the genetic code. Such small-scale changes can produce an entirely different amino acid or can end protein production altogether. Large changes, involving the deletion, rearrangement, or duplication of hundreds or even millions of nucleotides, can result in the elimination, misplacement, or duplication of entire genes. Some mutations are harmless, but others can cause disease or increase the risk of disease. As a result, the study of genetics can lead to valuable medical breakthroughs.

So, what do you think Scalia is objecting to? Is he just signaling that he thinks that the details of the molecular biology are not important here? Is it the claim that “Genes form the basis for hereditary traits in living organisms”? Is he unable to affirm with his own belief that G pairs with C? That uracil substitutes for thymine in RNA? That humans have 23 pairs of chromosomes?

Please share your most outlandish conspiracy theories in the comments!

I bet Fat Tony just HATES joining in a unanimous opinion with those uppity liberal women.

Just kidding. I have no idea what his problem is. (That’s a general proposition about Scalia, actually. He’s not an idiot, but he is a jerk.)

Anyhow, this ruling is long overdue. The patenting of naturally occurring genes is an absurdity, perhaps the most grotesque dysfunctionality of the the generally dysfunctional American patent system. Good riddance.

I feel a bit weird here, because, like you, I am no Scalia fan in general. However, I do think that the Gawker article was a bit unfair.

My honest best guess is that Scalia’s thought process was something along the lines of, “Well, that’s a lot of technical detail that does not need to be in there. I’m not going to waste my time learning about any of it, because, from a legal perspective, it does not matter.”

And when I think of it that way, I almost want to congratulate him for his intellectual honesty. (And that makes me feel dirty.)

Or maybe it was just a gratuitous smackdown of Thomas, like, “Well, that’s not how I would have written it.” Just sort of him being a dick — which sounds right to me.

It just seems so weird, in part because I assume that they are often hearing cases that include a lot of technical details, and that, quite often, none of the justices are experts in those details. Yet, I assume that sort of situation does not normally lead to one of them actually writing a separate opinion.

Well, straightforward, except we all have reverse transcriptase in some of our genomes, which when occasionally transcribed, produces a protein that may well make a cDNA, evidence of which is sometimes fossilized back our genome as a processed pseudo gene. So is cDNA naturally occurring? You bet. Is it the process of making that is relevant? Can’t be, because then companies could just end-run this ruling by making what they discovered. Or is it okay if you make something as long as you don’t know for absolute sure it exists in nature? In that case, patentability depends on the state of mind of the patent applicant. So I don’t see how cDNA can be upheld as a logically sound counter-example.

Yes, that’s an excellent point and question. They actually explicitly address the issue you bring up, albeit in a footnote:

8 Some viruses rely on an enzyme called reverse transcriptase to reproduce by copying RNA into cDNA. In rare instances, a side effect of a viral infection of a cell can be the random incorporation of fragments of the resulting cDNA, known as a pseudogene, into the genome. Such pseudogenes serve no purpose; they are not expressed in protein creation because they lack genetic sequences to direct protein expression. See J. Watson et al., Molecular Biology of the Gene 142, 144, fig. 7–5 (6th ed. 2008). Perhaps not surprisingly, given pseudogenes’ apparently random origins, petitioners “have failed to demonstrate that the pseudogene consists of the same sequence as the BRCA1 cDNA.” Association for Molecular Pathology v. United States Patent and Trademark Office, 689 F. 3d 1303, 1356, n. 5 (CA Fed. 2012). The possibility that an unusual and rare phenomenon might randomly create a molecule similar to one created synthetically through human ingenuity does not render a composition of matter nonpatentable.

So, they seem to hinge the distinction on 1) the (supposed) rarity of the phenomenon, and 2) the idea that pseudogenes tend to accumulate mutations.

It’s not clear to me what happens if someone patents a cDNA construct, and then someone else discovers a genomic insertion with identical sequence. Also, I assume the patents were on the “gene”, and were meant to cover multiple alleles — that’s the whole point of a genetic test, after all. So, what if, for example, a pseudogene differs from your cDNA construct, but only via synonymous substitutions?

The ruling definitely kicks a bunch of important questions down the road (as is the custom when it comes to Supreme Court rulings).